The hypothesis has been advanced that estrogen regulates growth and differentiation of the uterus by stimulating nuclear gene transcription. The synthesis of regulatory proteins appears to be initiated by the interaction of a specific nuclear receptor estrogen complex with the genome. An ordered sequence of transcription and translation follows. It will be an objective of this study to determine which of these processes is obligatory for the stimulation of uterine cellular hypertrophy and hyperplasia (true growth). The experiments detailed in this proposal will study the dynamics of translocation of the cytosol receptor estrogen complex to the nucleus, the specific binding of estrogen in the nucleus and the fate of nuclear bound estrogen. The question will be asked as to whether the sequence of events related to specific nuclear binding of the estrogen is obligatory to the expression of the biochemical processes which result in true uterine growth. Specifically, the nuclear events will be studied contemporaneously with various biochemical parameters of uterine growth, e.g., endogenous nuclear DNA-dependent RNA polymerases I and II, qualitative RNA and protein synthesis, composition and transcriptional capacity of chromatin. The analysis of these interrelated phenomena will provide insight into the biological action of various estrogens, each of which elicits a different pattern of uterine growth.